Methods and apparatus for therapeutic application of thermal energy including blood viscosity adjustment

ABSTRACT

Apparatus and methods are provided for treating a human condition by providing an appendage chamber having a thermal exchange member. Negative pressure may be applied to a human appendage when placed within the appendage chamber. Blood flowing through the arteriovenous anastomosis (AVA) of the appendage may be heated or cooled at the thermal exchange member for therapeutic application of thermal energy to adjust blood viscosity in the human to alleviate symptoms associated with a number of autoimmune, circulatory, neurological, lymphatic, and endocrinal maladies. A load sensor may be coupled to the thermal exchange member and configured to measure a force of the appendage applied to the thermal exchange member. In addition, a negative pressure sensor may measure pressure within the appendage chamber.

I. FIELD OF THE INVENTION

This application generally relates to therapeutic manipulation ofmammalian thermoregulation.

II. BACKGROUND OF THE INVENTION

The body temperature of mammals is normally tightly controlled by anautonomic regulatory system referred to herein as the thermoregulatorysystem. A primary effector of this regulatory system is blood flow tospecialized skin areas where heat from the body core may be dissipatedto the environment. Normally, when body and/or environmentaltemperatures are high, the dilation of certain blood vessels favors highblood flow to these skin areas, and as environmental and/or bodytemperatures fall, vasoconstriction reduces blood flow to these skinareas and minimizes heat loss to the environment.

Strategic inducement of vasodilation and heat transfer in targetedportions of the body, such as the extremities, may exert positivetherapeutic benefits in remote regions of the body. For example,manipulating heat transfer across the skin may change the coretemperature of the mammalian body in response. Unfortunately, it may bedifficult to induce such changes to an extent sufficient for therapy,given the human body's refined ability to thermoregulate to maintaintemperature homeostasis or normothermia.

By applying heat and subatmospheric (negative) pressure to a hypothermicindividual's skin, normothermia may be achieved (see, e.g., Grahn etal., “Recovery from mild hypothermia can be accelerated by mechanicallydistending blood vessels in the hand,” J. Appl Physiol. (1998)85(5):1643-8). Other therapeutic applications for cooling the skin toachieve normothermia have also been described; e.g., in treating canceras described in U.S. Pat. No. 7,182,776 to Grahn. However, therapeuticapplications for continuously applying heat to the skin while atnormothermia to increase microvascular circulation and/or to adjustblood viscosity have not been demonstrated.

Every year, millions of dollars are spent on treatments and drugs forreducing blood viscosity. Such drugs suffer from a variety of drawbacksincluding cost and side effects such as dizziness, headache, nausea,vomiting, chest pain, and irregular heartbeat.

In view of the foregoing drawbacks of previously known systems, it wouldbe desirable to provide a robust and economical system to increase wholebody circulation and to increase or decrease blood viscosity.

III. SUMMARY OF THE INVENTION

The present invention overcomes the drawbacks of previously-knownapparatus by providing apparatus for treating a condition of a humanthat includes an appendage chamber, a thermal exchange member, and apressure source. The appendage chamber may be configured to accept ahuman appendage, e.g., hand or foot, containing an arteriovenousanastomosis (AVA). The thermal exchange member is disposed within theappendage chamber and configured to selectively heat or cool bloodflowing through the AVA. The pressure source is coupled to the appendagechamber and configured to apply negative pressure within the appendagechamber.

In accordance with one aspect of the present invention, the apparatusmay include a load sensor coupled to the thermal exchange member andconfigured to measure a force of the appendage applied to the thermalexchange member. The load sensor may be electrically coupled to aprogrammable controller configured to: (a) determine a base forcemeasured using the load sensor, (b) calculate and set a force rangeusing the base force, (c) monitor whether the force of the appendagemeasured by the load sensor falls within the force range, (d) send analert if the force is outside the force range, and (e) adjust the forcerange over time to accommodate ambient temperature variations caused byheating or cooling the thermal exchange member.

In accordance with another aspect of the present invention, theappendage chamber may include an expandable cuff with an appendageopening configured to accept the appendage. The pressure source may becoupled to the expandable cuff and configured to apply positive pressureto expand, e.g., inflate, the expandable cuff to seal around theappendage. The apparatus may include a flexible membrane having amembrane opening configured to accept the appendage such that theflexible membrane conforms to the expandable cuff as the pressure sourceapplies positive pressure. The appendage chamber also may include apressure chamber insert (PCI) having the expandable cuff, wherein thePCI is configured to be removable from the appendage chamber.

The apparatus may include a sealing pad disposed within the appendagechamber and having a sealing pad opening configured to be disposedaround the thermal exchange member. The sealing pad is configured to becoupled to the PCI to enhance application of negative pressure withinthe PCI. The apparatus also may include a deformable pad disposed withinthe appendage chamber and configured to contact the appendage and theappendage chamber to urge the appendage onto the thermal exchangemember.

In accordance with one aspect of the present invention, the pressuresource is disposed within the appendage chamber, coupled to theexpandable cuff, and configured to apply positive pressure to expand theexpandable cuff to seal around the appendage and to apply negativepressure to the appendage when placed within the appendage chamber. Theapparatus may include a negative pressure sensor configured to measure apressure within the appendage chamber. The negative pressure sensor maybe electrically coupled to a programmable controller configured tomonitor the pressure measured by the negative pressure sensor and directthe pressure source to expand the expandable cuff if the measuredpressure is above a predetermined pressure

The thermal exchange member may include a Peltier device or electricheating device coupled to a metal or plastic pad and configured to heator cool the thermal exchange member. The thermal exchange member alsomay include electrical heating components. The thermal exchange membermay be configured to be heated to a suitable temperature, e.g., between107-110° F. or between 100-120° F., or cooled to a suitable temperature,e.g., between 58-64° F. or between 58-95° F., or both. In oneembodiment, the thermal exchange member is configured to heat or coolthe blood at a temperature and for a duration sufficient to adjust theviscosity of blood in the human.

The programmable controller may be configured to control the applicationof negative pressure within the appendage chamber, e.g., within the PCI,and may be configured to monitor application of negative pressure withinthe appendage chamber responsive to the pressure measured by thenegative pressure sensor. The programmable controller further isconfigured to control heating or cooling of the thermal exchange memberresponsive to user input or a preselected therapy regime. Thepreselected therapy regime may be selected to alleviate a symptomassociated with an autoimmune, circulatory, neurological, lymphatic,thermoregulatory disorders, or endocrinal dysfunction, or anycombination thereof including, but not limited to, Parkinson's disease,diabetic neuropathy, migraine headaches, Alzheimer's disease,fibromyalgia, Lyme disease, bipolar disorder, schizophrenia, attentiondeficit disorder (ADD), attention deficit hyperactivity disorder (ADHD),obsessive compulsive disorder (OCD), and Autism.

In accordance with another aspect of the present invention, a method foradjusting viscosity of blood is provided. The method may includeproviding an appendage chamber, a thermal exchange member disposedwithin the appendage chamber, and a pressure source coupled to theappendage chamber; disposing a human appendage containing anarteriovenous anastomosis (AVA) within the appendage chamber; applyingnegative pressure in the appendage chamber using the pressure source;and heating or cooling the thermal exchange member to deliver heating orcooling to blood flowing through the AVA at a temperature and for aduration sufficient to adjust the viscosity of the blood to alleviate asymptom associated with at least one of an autoimmune, circulatory,neurological, lymphatic, thermoregulatory, or endocrinal malady.

The heating or cooling may include heating or cooling the thermalexchange member to deliver heating or cooling for approximately five tothirty minutes.

In one embodiment, negative pressure is applied in the appendagechamber, and optionally in the PCI, using the pressure source andmaintaining the negative pressure between −20 mmHg and −40 mmHg orbetween −1 mmHg and −50 mmHg.

The adjustment in viscosity of blood may increase microvascularcirculation and alleviate a symptom associated with hypertension,occlusive arterial disease, myocardial infarction, kidney failure, liverfailure, hyperglycemia, preeclampsia, dyslipidemia, and diseases orconditions associated with systemic inflammation or hyperviscosity ofthe blood.

IV. BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a perspective view of an exemplarily apparatus for treating acondition constructed in accordance with one aspect of the presentinvention.

FIG. 1B is a perspective, partially exploded view of the exemplaryapparatus of FIG. 1A.

FIG. 1C is another perspective, partially exploded view of the exemplaryapparatus of FIG. 1A.

FIG. 1D is a bottom view of the exemplary apparatus of FIG. 1A with partof the lower housing removed for clarity.

FIG. 2 is a perspective view of an exemplary pressure chamber insert andan exemplary flexible membrane constructed in accordance with one aspectof the present invention.

FIG. 3 is a schematic view of an apparatus for treating a conditionusing thermal energy constructed in accordance with one aspect of thepresent invention.

FIG. 4 is a flowchart depicting a method for determining and adjusting aforce range measured at the thermal exchange member in accordance withthe methods of the present invention.

FIG. 5 is a flowchart depicting a method for applying positive andnegative pressures in accordance with the methods of the presentinvention.

FIG. 6 is a flowchart depicting a method for monitoring pressure andadjusting pressure within the apparatus in accordance with the methodsof the present invention.

FIGS. 7A and 7B are images from a microscope of red blood cells within ablood sample from a patient treated in accordance with methods of thepresent invention, before and after treatment, respectively.

FIGS. 8A and 8B are images from a microscope of red blood cells within ablood sample from another patient treated in accordance with methods ofthe present invention, before and after treatment, respectively.

V. DETAILED DESCRIPTION OF THE INVENTION

The present invention provides methods and apparatus for applyingthermal energy to a human to increase or rebalance blood circulation,and/or stimulate the lymphatic or endocrine systems to address a varietyconditions. The methods and apparatus of the present invention areexpected to provide beneficial results in treating a number of commonailments, including improved healing of acute and chronic wounds, andrelief from neurological and hormone-relating ailments as described inU.S. Patent Application Publication No. 2012/0191022 to Muehlbauer,assigned to the assignee of the present invention, the entire contentsof which are incorporated herein by reference.

In accordance with one aspect of the present invention, apparatus isprovided that includes an appendage chamber, a pressure source, and athermal exchange member. In one embodiment, the apparatus provides anegative pressure environment that assists in maintaining vasodilationand enhances the transfer to energy to an arteriovenous anastomosis(AVA) vascular area of the palm of a human hand. The AVA vascular areamay experience vasodilation from pre-treatment hyper-normothermia and/orheat delivered to the area from the thermal exchange member duringtreatment. This vasodilation increases the heat exchange between thethermal exchange member and the circulatory system by increasing bloodflow within the palm AVA's. An appendage chamber, e.g., clam shell,glove-like, boot-like, or sleeve-like chamber, may be used to provide anegative pressure environment while providing heating or cooling to anappendage using a thermal exchange system for a preselected time, e.g.,between approximately 5 and 30 minutes. While embodiments of theinvention will be described further below with respect to a chamberconfigured to receive a hand, it is recognized that the appendagechamber may be adapted for use with other appendages containing an AVAsuitable for the vasodilation methods described herein, such asvasculatures in the foot.

The present invention further provides methods and apparatus forapplying thermal energy to a human to increase or decrease bloodviscosity to address a variety of medical conditions such as autoimmune,circulatory, neurological, lymphatic, and endocrinal maladies.

Apparatus Overview

Referring to FIGS. 1A, 1B, 1C, and 1D, apparatus 100 for treating acondition is provided, including appendage chamber 102, thermal exchangemember 104, and control panel 106. Appendage chamber 102 includes ahousing configured to accept a human appendage containing an AVA such asa hand, for example, through appendage opening 108. In preferredembodiments, appendage chamber 102 comprises a durable and relativelyrigid plastic or metal alloy, or combination thereof, of whichindividual components may be formed using conventional injection-moldingor stamping processes. Appendage chamber 102 preferably includespressure chamber insert (PCI) 110 that may be partially or fullytransparent such that a user and/or physician may monitor the handduring treatment. Preferably, PCI 110 comprises a rigid, substantiallytransparent plastic or polymer, such as polycarbonate, which allows theuser or care-giver to visualize placement of the hand within thechamber.

Thermal exchange member 104 may be disposed within appendage chamber 102and may comprise a plastic, biocompatible metal, such as aluminum, metalalloy, or the like. Thermal exchange member 104 is configured toselectively heat or cool blood flowing through the AVA of the appendagedisposed within appendage chamber 102. For example, thermal exchangemember 104 may be configured to be heated to approximately 107.4° F.,108.4° F., 109.4° F., between 107-110° F., between 105-112° F., orbetween 100-120° F. and may be configured to be cooled to approximately60.8° F., between 60-62° F., between 58-64° F., or between 58-95° F. Inone embodiment, thermal exchange member 104 comprises a Peltier deviceconfigured to heat and/or cool thermal exchange member 104. Thermalexchange member 104 also may include suitable components for resistiveheating such as a conductive wire configured to receive an electricalcurrent and release heat. Thermal exchange member 104 may be shaped andsized to contact an appendage, for example, a palm of the hand. In oneembodiment, thermal exchange member 104 includes palm pad 112 (shown inFIG. 1B) that extends outwardly from thermal exchange member 104 topromote enhanced contact with the palm.

Control panel 106 is configured to provide a user interface for a userand/or clinician or care-giver to control operations of apparatus 100.Control panel 106 may include buttons, assorted lighting sources, e.g.,LEDs, and/or a display, e.g., an LCD or LED readout, that may be a touchscreen. Illustratively, control panel 106 includes display 114, on/offbutton 116, on/off LED 118, ready symbol 120, ready LED 122, left button124, right button 126, up button 128, down button 130, and accept button132.

Appendage chamber 102 may include a plurality of feet 134, 136 coupledto appendage chamber base 138. Feet 134, 136 may be configured to beadjusted to raise or lower a portion of appendage chamber 102. Forexample, rear feet 136 may be adjusted to increase the distance betweenrear feet 136 and base 138, thereby raising the rear portion ofapparatus 100. In one embodiment, feet 136 are coupled to base 138 via athreaded male member that is screwed into a threaded female member inappendage chamber 102 to adjust the distance between feet 136 and base138. Advantageously, a user may adjust feet 136 such that appendageopening 108 is angled in a manner that the user may insert their handinto appendage opening 108 and comfortably rest their elbow on asurface, e.g., table, desk, or medical cart, holding apparatus 100.

As depicted in FIG. 1B, PCI 110 may include appendage opening 108, cuff140, expandable cuff 142, cuff seal 144, PCI edges 146, PCI base 148,PCI base opening 150, and PCI positive pressure input 152. Cuff 140 maycomprise a plastic, biocompatible metal, such as aluminum, metal alloy,or the like and is shaped and sized to accept an appendage throughappendage opening 108. Illustratively, cuff 140 is elliptically shapedalthough, as would be understood by one of ordinary skill in the art,cuff 140 may take other shapes including a rectangle or a rectangle withrounded corners. Cuff 140 is coupled to expandable cuff 142. Expandablecuff 142 is configured to expand to seal around an appendage placedwithin PCI 110 through appendage opening 108. Expandable cuff 142 maycomprise a rubber, such as latex, nitrile, or neoprene, and/or plastic,such as polyvinyl chloride, polyethylene, or polyurethane and may bebetween 5-20 mil thick, preferably about 8 mil. Cuff 140 may be coupledto the main body of PCI 110 via cuff seal 144. Cuff seal 144 isconfigured to couple cuff 140 to the main body of PCI 110, and maycomprise a suitable adhesive material such as silicon. Cuff 140optionally may be removable from PCI 110.

In accordance with one aspect of the present invention, PCI 110 isconfigured to be removable from appendage chamber 102. PCI 110 may becoupled to appendage chamber by placing PCI edges 146 on chamber ledges154 of appendage chamber 102 such that PCI base 148 contacts appendagechamber 102, optionally at sealing pad 158, and thermal exchange member104 is disposed within PCI base opening 150. PCI positive pressure input152 is configured to be disposed within chamber aperture 156 ofappendage chamber 102.

Apparatus 100 further may include sealing pad 158 that is configured tocouple to PCI base 148 to maintain negative pressure within PCI 110.Sealing pad 158 is disposed within appendage chamber 102 and includessealing pad opening 160 through which thermal exchange member 104extends. Preferably, sealing pad 158 comprises a deformable, sponge-likeor foam-like material that supports PCI base 148 when it contactssealing pad 158 to create an air-tight seal. In one embodiment, sealingpad 158 includes a groove that accepts PCI base 148 therein.

Pressure source 162 and circuitry housing 164 having a programmablecontroller coupled thereto may be disposed within appendage chamber 102.Pressure source 162 is a suitable device for pumping fluid, e.g., air,and for creating and maintaining negative pressure in appendage chamber102 at a suitable pumping rate, e.g., greater than about 4 liters perminute. In one embodiment, pressure source 162 is a diaphragm pump.Pressure source 162 may be configured to apply positive pressure toexpand expandable cuff 142 to seal around an appendage placed therein bypumping a fluid into expandable cuff 142. Pressure source also may beconfigured to apply negative pressure within appendage chamber 102,including PCI 110, and to create an air-tight seal between PCI base 148and sealing pad 158 when an appendage is placed therein. Pressure source162 may be coupled to expandable cuff 142 via a pressure line coupledbetween pressure source 162 and PCI positive pressure input 152. In oneembodiment, pressure source 162 is configured to maintain the negativepressure within the appendage chamber between −20 mmHg and −40 mmHg orbetween −1 mmHg and −50 mmHg. Pressure source 162 assists in maintainingvasodilation and to enhance the transfer to energy to an arteriovenousanastomosis vascular area of the appendage, e.g., located in the palm ofa hand. The arteriovenous anastomosis vascular area may experiencevasodilation from pre-treatment hyper-normothermia and/or heat deliveredto the area from thermal exchange member 104 during treatment.

Appendage chamber 102 may include power interface 166 that connects toan AC or DC power source to power apparatus 100 and/or charge at leastone battery within appendage chamber 102. In one embodiment, apparatus100 is powered with at least one replaceable battery and power interface166 may be omitted.

Appendage chamber 102 may further include a plurality of vent holes 168configured to expel heat resulting from operation of apparatus 100therethrough.

As illustrated in FIG. 1C, apparatus 100 further may include deformablepad 170. Deformable pad 170 is configured to be disposed withinappendage chamber 102, and specifically, within PCI 110. Deformable pad170 may be coupled to upper surface 172 within PCI 110 via a suitableadhesive, VELCRO® coupling, or like. Preferably, deformable pad 170comprises a deformable, sponge-like or foam-like material that contactsan appendage and appendage chamber 102, specifically upper surface 172within PCI 110, to urge the appendage onto thermal exchange member 104.Advantageously, deformable pad 170 may be utilized to urge an appendageonto thermal exchange member 104 of a person unable to hold theirappendage onto thermal exchange member 104 because, for example, theyare unconscious. As shown in FIG. 1C, PCI 110, sealing pad 158, and/ordeformable pad 170 may be removable from appendage chamber 102.

FIG. 1D illustrates a bottom view of apparatus 100 with part of thelower housing and circuit board removed for clarity. Appendage chamber102 includes relief valve 174 coupled to expandable cuff 142 andconfigured to release fluid, e.g., air, within expandable cuff 142 whenrelief valve 174 is depressed for pressure relief. Appendage chamber 102further includes pressure pole 176 coupled to thermal exchange member104. Pressure pole 176 displaces load sensor 190 (described below) whena force is applied to thermal exchange member 104, such that the appliedforce may be measured as described in detail below. Appendage chamber102 further includes negative pressure opening 178 beneath thermalexchange member 104 such that pressure source 162 may apply negativepressure within appendage chamber 102, including within PCI 110, throughnegative pressure opening 178. Negative pressure opening 178 may span asubstantial area beneath the base of the thermal exchange member 104,e.g., over 60% of the area.

In one embodiment, apparatus 100 further includes a circuit boarddisposed beneath thermal exchange member 104. The circuit board maypermit application of negative pressure within appendage chamber 102,e.g., within PCI 110 through negative pressure opening 178, via pressuresource 162.

Referring now to FIG. 2, exemplary PCI 110 and flexible membrane 180 areillustrated in accordance with the present invention. Flexible membrane180 is suitably sized to receive an appendage, e.g., a hand, wrist andforearm. Illustratively, flexible membrane 180 is generally tubularshaped, although it may be glove or mitt shaped, and includes membraneopening 182 that is configured to accept the appendage. Flexiblemembrane 180 may comprise a flexible and durable material, such asneoprene, that may be used with different patients. Alternatively, forsanitary purposes, flexible membrane 180 may be disposable and designedfor one-time use. In this case, flexible membranes 180 having differentsizes may be supplied with apparatus 100 to reduce cross-contaminationif the device is used by multiple patients. Preferably, flexiblemembrane 180 comprises a light weight plastic, such as polyethylene orpolyurethane, and is disposable after a single use reducing thepotential for spread of bacteria or viruses in cases where multipleusers use apparatus 100, such as hospital or nursing home settings.Provided that the material comprising flexible membrane 180 issufficiently thin, e.g., 0.5 mil, flexible membrane 180 is expected toprovide adequate heat transfer between the palm of the hand and thermalexchange member 104. Flexible membrane 180 may include pressureequalizing vent(s) 184 configured to permit a fluid, e.g., air, to bedrawn from within flexible membrane 180 through vents 184 as negativepressure is applied via pressure source 162 to create a negativepressure environment within flexible membrane 180. Flexible membrane 180is further configured to conform to expandable cuff 142 as pressuresource 162 applies positive pressure to expand expandable cuff 142 whenflexible membrane is disposed within appendage opening 108.

Flexible membrane 180 may further include a sealing member, e.g., arubber O-ring, an elastic band, an attached VELCRO® strap, or the like,configured to tighten flexible membrane 180 around a portion of a user'sappendage, e.g., wrist or forearm.

Flexible membrane 180 is configured to be at least partially disposedwithin appendage chamber 102, and specifically PCI 110, and may beremovable from appendage chamber 102.

Referring now to FIG. 3, a schematic illustrating the internalcomponents of the embodiment of apparatus 100 is described. Programmablecontroller 186 may be electrically coupled to, and configured tocontrol, thermal exchange member 104, control panel 106, temperaturesensor 188, load sensor 190, pressure source 162, negative pressuresensor 192, power source 194, communication unit 196, and/or pulseoximeter 198.

Programmable controller 186 may include one or more microprocessors,controllers, digital signal processors (DSPs), application specificintegrated circuits (ASICs), field-programmable gate arrays (FPGAs), orequivalent discrete or integrated digital or analog logic circuitry, andthe functions attributed to programmable controller 186 herein may beembodied as software, firmware, hardware, or any combination thereof.Programmable controller 186 may include a memory for storing datarelated to use of apparatus 100, such as user input, treatment times,treatment settings, detected errors, and the like. The memory may storeprogram instructions that, when executed by programmable controller 186,cause programmable controller 186 and apparatus 100 to provide thefunctionality ascribed to them herein. The memory of programmablecontroller 186 also may store software downloaded thereon or implementedas a program product and stored on a tangible storage device such asmachine-readable medium, e.g., tape, compact disk (CD), digitalversatile disk (DVD), blu-ray disk (BD), external nonvolatile memorydevice, USB, cloud storage, or other tangible storage medium. Thesoftware may include computer executable instructions for controllingapparatus 100.

Programmable controller 186 also may store in its memory therapyprograms directed to treatment of specific maladies. For example, anembodiment of apparatus 100 intended for use in a nursing home settingmay include programs for increasing whole body circulation to addressneurological ailments, such as migraine headaches, or circulatoryissues, such as chronic wounds or reduced peripheral blood flowresulting from diabetes or immobility. In this context, apparatus may beused by a number of nursing home residents to provide relief from suchailments, and include preprogrammed therapeutic regimes (e.g.,appropriate temperature adjustments for preselected durations) suitablefor treating such residents. Preselected programs stored in apparatus100 may be loaded at the manufacturer, or generated using a suitablesoftware program on a conventional personal computer and then uploadedto memory associated with programmable controller 186 via a data port,e.g., USB port, on appendage chamber 102 or communication unit 196,described below. The data port further may be used to retrieve and/orstore data on a tangible storage device related to use of apparatus 100,such as user input, treatment times, treatment settings, detectederrors, and the like.

Programmable controller 186 preferably also includes preprogrammedsafety features, e.g., that shutdown the device if the apparatussensors, such as the temperature and negative pressure sensors, fail orbecome disconnected. Programmable controller 186 also may include anerror circuit that displays error codes on control panel 106.

The electronics of apparatus 100 are coupled to control panel 106, sothat programmable controller 186 actuates apparatus 100 in accordancewith input commands or selection of pre-programmed therapy regimes inputvia control panel 106. For example, referring to FIG. 1A, whenprogrammable controller 186 detects that left button 124 or right button126 is pressed, programmable controller 186 directs thermal exchangemember 104 to decrease or increase temperature, respectively. As anotherexample, when programmable controller 186 detects that up button 128 ordown button 130 is pressed, programmable controller 186 directs a clockapplication to increase or decrease, respectively, a countdown timer fortreatment.

Referring back to FIG. 3, programmable controller 186 is configured todirect thermal exchange member 104 to heat or cool to a temperatureresponsive to user input at control panel 106 or to a preselectedtherapy regime. In one embodiment, programmable controller 186 isprogrammed to heat thermal exchange member to a high, medium, or lowtemperature, e.g., 109.4° F., 108.4° F., or 107.4° F., respectively,based on user input received at control panel 106. Programmablecontroller 186 further may include a clock application that directsthermal exchange member to heat or cool at the temperature for a time,e.g., 5, 10, 15, 20, 25, or 30 minutes, responsive to user input atcontrol panel 106 or to a preselected therapy regime.

Temperature sensor 188 is a suitable temperature sensor, e.g., athermocouple, that may be disposed adjacent to or within thermalexchange member 104. Temperature sensor 188 is configured to sense atemperature at thermal exchange member 104. Temperature sensor 188 maybe operatively coupled to programmable controller 186 to regulateheating or cooling to maintain thermal exchange member 104 atsubstantially a target temperature that may be preprogrammed or inputvia control panel 106.

Load sensor 190 is a suitable force sensor, e.g., a load cell orpressure transducer, and may be disposed adjacent to or within thermalexchange member 104. Load sensor 190 is configured to measure a force,e.g., a force of a user's hand, applied to thermal exchange member 104.Advantageously, thermal exchange member 104 and load sensor 190 areconfigured to accommodate many different sizes of hands, including thoseof unconscious patients, while minimizing the risks of discomfort orvasoconstriction. Force measured at load sensor 190 may be used byprogrammable controller 186 to determine if a hand is placed too lightlyon thermal exchange member 104, thereby reducing energy transfer, orplaced too heavily, thereby inducing vasoconstriction of the vasculatureof the palm, also reducing energy transfer. As explained below, an alertat control panel 106 may be audibly or visibly displayed if the measuredforce is not within a predetermined range, e.g., too high or too low, toalert a user/caregiver/physician.

As explained above, pressure source 162 is configured to apply positivepressure to expand expandable cuff 142 and to apply negative pressurewithin appendage chamber 102 and to assist in maintaining vasodilatationof, and to enhance energy transfer to, an appendage when placed withinappendage chamber 102. In one embodiment, pressure source 162 isconfigured to apply negative pressure within appendage chamber 102 and,specifically, within PCI 110 to create an air-tight seal between PCIbase 148 and sealing pad 158. Pressure source 162 may be coupled toappendage chamber 102 via a pressure line that is coupled to negativepressure check valve 191. Negative pressure check valve 191 isconfigured to open to allow the release of excess negative pressure frompressure source 162. In addition, pressure source 162 may be coupled toexpandable cuff 142 via a pressure line that is coupled to positivepressure check valve 193. Positive pressure check valve 193 isconfigured to open to allow the release of excessive positive pressurefrom expandable cuff 142.

Negative pressure sensor 192 may be coupled to appendage chamber 102.Negative pressure sensor 192 is a suitable pressure sensor and isconfigured to measure the pressure within appendage chamber 102 andspecifically, within PCI 110, to output a signal to programmablecontroller 186 that is used to achieve a preselected negative pressure,e.g., between −20 mmHg and −40 mmHg or between −1 mmHg and −50 mmHg,within PCI 110. Programmable controller 186 is configured to monitorapplication of negative pressure within PCI 110 responsive to pressuremeasured by negative pressure sensor 192. In one embodiment, pressuresource 162 is coupled to a pressure relief valve, e.g., via a pressureline, that is configured to release excess pressure at a predeterminedpressure, e.g., lower than −50 mm Hg, −80 mm Hg, or −100 mm Hg, shouldnegative pressure sensor 192 or programmable controller 186 malfunction.

Power source 194 may be a port, e.g., power interface 166, to allowapparatus 100 to be plugged into a conventional wall socket, e.g., via acord with an AC to DC power converter, for powering components withinthe housing. Alternatively, power source 194 may be a suitable batterysuch as a replaceable battery or rechargeable battery and apparatus mayinclude circuitry for charging the rechargeable battery, and adetachable power cord.

Communication unit 196 is configured to transmit information, such asuser input, treatment times, treatment settings, detected errors, andthe like, to a remote location such as a doctor workstation.Communication unit 196 is configured for wired and/or wirelesscommunication over a network such as the Internet or a telephone networkusing techniques known in the art. Advantageously, communication unit196 permits a doctor, caregiver, user, and the like to monitor use ofapparatus 100.

Optionally, apparatus 100 may include pulse oximeter 198 configured tomonitor oxygen saturation of a user's blood using components known inthe art. In one embodiment, components including a light emitter, e.g, apair of LEDs, and a light receiver, e.g., a photodiode, are disposedwithin appendage chamber 102 for monitoring oxygen saturation and bloodvolume during a treatment by apparatus 100. Programmable controller 186may direct control panel 106 to display pulse oximetry information,e.g., oxygen saturation levels, pulse rate, photoplethysmograph, etc.,or may direct communication unit 196 to transmit the pulse oximetryinformation to a remote location.

In alternative embodiments, one or more of the components suppliedwithin appendage chamber 102 may be omitted. For example, an embodimentof apparatus 100 suitable for use in a hospital, where suction lines arereadily available in the patient rooms, may omit pressure source 162 andinstead use the “house” suction system.

Methods of Using the Apparatus

Methods of using apparatus for the therapeutic application of thermalenergy will now be described with reference to FIGS. 1A through 3.

Apparatus 100 may be used to treat a variety of conditions believed toarise from deficiencies of the autoimmune, circulatory, lymphatic andendocrine systems, and which may beneficially impact neurologicaldeficits as well. It is expected, for example, that use of the apparatusof the present invention may treat or alleviate a variety of ailments asdescribed in U.S. Patent Application Publication No. 2012/0191022 toMuehlbauer, and others including: improved healing for acute and chronicwounds and post-operative conditions; relief for respiratory conditionssuch as asthma; sleeping conditions such as snoring and sleep apnea;metabolic disorders such as hypothyroidism; obesity; chronic fatiguesyndrome; certain autoimmune disorders; Raynaud's phenomenon; hotflashes; edema; renal disease; cirrhosis; allergies; neurologicalmaladies such as Parkinson's disease, diabetic neuropathy, migraines,Alzheimer's disease, bipolar disorder, schizophrenia, attention deficitdisorder (ADD), attention deficit hyperactivity disorder (ADHD),obsessive compulsive disorder (OCD), and Autism; circulatory disordersassociated with vasoconstriction such as hypertension, carpal tunnelsyndrome, trigger finger, and arthritis; diabetes; dermatologicaldisorders associated with restricted blood flow to the skin such aseczema; disorders known to disrupt thermoregulatory processes such asstress and anxiety; neurodegenerative conditions such as multiplesclerosis and fibromyalgia; increased fetal circulation duringpregnancy; and sequalae of chemotherapy (affecting digestion) andirritable bowel syndrome (affecting bowel regularity). Apparatus 100also may be used to enhance delivery of drugs by increasing bodycirculation.

Applicant has discovered that apparatus 100 also may be used to reducecore body temperature for treatment of heart attack, stroke, heatstroke, and fever including fever not resulting from an immune response.Applicant has additionally discovered that apparatus 100 may be used toadjust blood viscosity to alleviate a symptom(s) associated with alldiseases or conditions associated with systemic inflammation orhyperviscosity of the blood.

In operation, a user or clinician activates apparatus 100 using controlpanel 106 and selects a heating or cooling mode, or if available, one aplurality of preprogrammed therapeutic regimes. Pushing on/off button116 activates power to apparatus 100 via power source 194 and turns onon/off LED 118 to indicate that the apparatus is powered on. After thecontroller power is activated, the system begins preheating thermalexchange member 104, LED 122 is activated to amber. Once thermalexchange member 104 is preheated to the desired temperature, ready LED122 is activated to green. In one embodiment, if a user desires to entera standby mode, the user may provide certain user input at control panel106, e.g., holding down accept button 132 and pressing on/off button 116at the same time. In standby mode, programmable controller 186 directsthermal exchange member 104 to heat to a standby temperature, e.g., 100°F., for a predetermined standby time, e.g., 4 hours, or until the userprovides input to deactivate standby mode.

Before, during, or after the preheat process, a user may provide userinput at control panel 106 regarding selection of a treatment time,treatment temperature, and/or therapy regime selection. A user mayinsert their appendage into flexible membrane 180 via membrane opening182. The user then may contact a portion of the appendage, e.g., a palmof their hand, to thermal exchange member 104.

Display 114 of control panel 106 may display a request that the userpress accept button 132 when flexible membrane 180 is secured around theappendage and positioned with appendage chamber 102. Once accept button132 is pressed, programmable controller 186 directs pressure source 162to apply positive pressure to expandable cuff 142 to seal around theappendage and to apply negative pressure within appendage chamber 102,for example, in PCI 110 via negative pressure opening 178. After apredetermined amount of time, e.g., 1 minute, programmable controller186 communicates with negative pressure sensor 192 regarding pressuresensed by negative pressure sensor 192. If the pressure indicates that asuitable pressure was not reached, programmable controller 186 directscontrol panel 106 to alert the user and may power down apparatus 100.Alternatively, if the pressure indicates that a suitable pressure wasreached, the programmed routine continues.

Programmable controller 186 may monitor the force applied by theappendage to thermal exchange member 104 via load sensor 190 tocalibrate the appropriate force for the appendage on an individual basisfor each user. In one embodiment, programmable controller 186 reads theforce values measured at load sensor 190 a predetermined number oftimes, e.g., 10 times, at a predetermined sampling rate, e.g., 0.25seconds between samples. If all of the measured force values are withina predetermined threshold, e.g., within 75% of the high/low thresholdfor the average value of the measured force values, then the calibrationwill pass. If one of the measured force values is outside thepredetermined threshold, the calibration will fail and programmablecontroller 186 will direct display 114 to display that the user shouldlift the appendage off thermal exchange member 104 for recalibration.

After the calibration process is completed, a user may begin to receivetreatment at the selected temperature setting and for the selected time.Thermal exchange member 104 may deliver heating or cooling to bloodflowing through the AVA at a temperature and for a duration sufficientto alleviate symptoms associated with a condition or disease. In oneembodiment, display 114 displays a countdown timer indicative of thetime remaining in a treatment and an indication of the currenttemperature setting.

During treatment, programmable controller 186 polls control panel 106 todetermine if a user provides input during treatment and, if so, directsthe appropriate component to respond to the user input. Also duringtreatment, programmable controller 186 polls temperature sensor 188,load sensor 190, and negative pressure sensor 192. If temperature sensor188 senses that thermal exchange member 104 is not maintaining theselected temperature, programmable controller 186 directs display 114 todisplay a heater error message. If load sensor 190 senses that themeasured force falls outside a predetermined range from the calibratedforce value, programmable controller 186 directs control panel 106 toaudibly alert and directs display 114 to display a message notifying auser to press down on thermal exchange member 104 if the force is toolow or display a message notifying a user to lift up from thermalexchange member 104 if the force is too high. If negative pressuresensor 192 senses that the pressure within appendage chamber is outsidea predetermined range, programmable controller 186 directs control panel106 to audibly or visibly alert a user that the pressure seal is lost.In addition, as described in detail below, programmable controller 186may monitor pressure measured by negative pressure sensor 192 and directpositive pressure source to expand expandable cuff 142 if the measuredpressure is outside a predetermined range, e.g., above a predeterminedpressure.

When the time for treatment is completed, programmable controller 186directs apparatus 100 to power down one or more components, e.g.,thermal exchange member 104, negative pressure sensor 192, power source194, if standby mode is off and directs apparatus 100 to enter standbymode if standby mode is on keeping thermal exchange member 104 inpreheat mode. The user may then break expandable cuff 142 seal bydepressing relief valve 174 and withdrawing the appendage from appendagechamber 102.

Referring now to FIG. 4, apparatus and method 200 for determining andadjusting a force range measured at thermal exchange member 104 are nowdescribed. As will be apparent to one of ordinary skill in the art,method 200 may be embodied in program instructions stored on the memoryof programmable controller 186 of FIG. 3 that, when executed byprogrammable controller 186, cause programmable controller 186 andapparatus 100 to provide the functionality ascribed to them herein. Theprogram instructions may be firmware or software downloaded onto thememory of programmable controller 186 or implemented as a programproduct and stored on a tangible storage device such as machine-readablemedium, e.g., tape, compact disk (CD), digital versatile disk (DVD),blu-ray disk (BD), external nonvolatile memory device, USB, cloudstorage, or other tangible storage medium.

At 202, programmable controller 186 determines a base force measuredusing load sensor 190 of an appendage on thermal exchange member 104. Inone embodiment, the base force is determined to be the average of themeasured force values from the calibration process described above. Inthat embodiment, programmable controller 186 reads the force valuesmeasured at load sensor 190 a predetermined number of times, e.g., 10times, at a predetermined sampling rate, e.g., 0.25 seconds betweensamples. If all of the measured force values are greater than zero andwithin a predetermined threshold, e.g., within 75% of the high/lowthreshold for the average value of the measured base force values, thenthe calibration will pass and the base force will be that average value.If one of the measured force values is outside the predeterminedthreshold, the calibration will fail and programmable controller 186will direct control panel 106 to audibly alert and direct display 114 todisplay a message notifying a user to press down on thermal exchangemember 104 for recalibration if the force is too low or display amessage notifying a user to lift up from the thermal exchange member 104for recalibration if the force is too high.

At 204, programmable controller 186 calculates and sets a force rangeusing the base force measured at 202. In one embodiment, programmablecontroller 186 calculates and sets the force range using a lookup tablestored in the controller's memory that includes an optimal energytransfer range including a low threshold and a high threshold for a baseforce. In another embodiment, programmable controller 186 calculates andsets the force range by multiplying the base force by a predeterminednumber, e.g., 0.75, to calculate the low threshold and multiplying thebase force by a different predetermined number, e.g., 1.25, to calculatethe high threshold of the force range. In yet another embodiment,programmable controller 186 calculates and sets the force range bysubtracting a predetermined number from the base force to calculate thelow threshold and adding a predetermined number, which may be the sameor different, to the base force to calculate the high threshold of theforce range.

At 206, programmable controller 186 monitors whether the force of theappendage on thermal exchange member 104 measured by load sensor 190falls within the force range calculated and set at 204. Preferably,programmable controller 186 monitors the force of the appendage during atreatment at a predetermined sampling rate.

If programmable controller 186 detects that the force measured in 206 isoutside the force range, programmable controller 186 directs apparatus100 to send an alert to the user/physician/caregiver, at 208. Sending analert may include directing control panel 106 to visibly and/or audiblyalert the user. In one embodiment, if programmable controller 186detects that the measured force is below the force range, display 114displays text to request a user to press down and if programmablecontroller 186 detects that the measured force is above the force range,display 114 displays text to request a user to lift up. Sending an alertmay also include shutting down power to one or more components toapparatus 100 such thermal exchange member 104, pressure source 162,and/or power source 194.

After alerting the user/physician/caregiver in 208, programmablecontroller 186 returns to 206 to monitor whether the measured force ofthe appendage is within the force range. If not, programmable controller186 may continue to send alerts to the user/physician/caregiver and, inone embodiment, may shut down one or more components to apparatus 100 ifa predetermined number of display alerts are sent.

If programmable controller 186 detects that the force measured in 206 iswithin the force range, programmable controller 186 adjusts the forcerange over time, at 210. In one embodiment, programmable controller 186adjusts the force range over time using an algorithm stored in thecontroller's memory. Programmable controller 186 may adjust the forcerange after a predetermined time interval, e.g., every 5 minutes, usinga lookup table stored in the controller's memory. Advantageously,adjusting the force range over time accommodates for ambient temperaturevariations caused by heating or cooling thermal exchange member 104.

Referring now to FIG. 5, apparatus and method 220 for applying positiveand negative pressures within apparatus 100 are now described. As willbe apparent to one of ordinary skill in the art, method 220 may beembodied in program instructions stored on the memory of programmablecontroller 186 of FIG. 3 that, when executed by programmable controller186, cause programmable controller 186 and apparatus 100 to provide thefunctionality ascribed to them herein. The program instructions may befirmware or software downloaded onto the memory of programmablecontroller 186 or implemented as a program product and stored on atangible storage device such as machine-readable medium, e.g., tape,compact disk (CD), digital versatile disk (DVD), blu-ray disk (BD),external nonvolatile memory device, USB, cloud storage, or othertangible storage medium.

At 222, apparatus 100 is powered on and a therapy session is initiatedbased on user input, as described above. For example, a user may selecta treatment time, a heating or cooling mode, or if available, aplurality of preprogrammed therapeutic regimes.

Programmable controller 186 reads the therapy countdown timer of theclock application, at 224. At 226, if the countdown timer is at zero,programmable controller 186 directs apparatus 100 to B, shown in FIG. 5,after which programmable controller 186 directs the pump motor ofpressure source 162 to turn off, directs the pump timer to reset, andterminates the therapy session, as described below. Alternatively, ifthe countdown timer is greater than zero, programmable controller 186reads the pressure measured by negative pressure sensor 192, at 228. If,at 230, the measured pressure read by programmable controller 186 isless than or equal to a predetermined pressure, programmable controller186 directs the pump motor of pressure source 162 to turn off, directs apump timer to reset, and returns to 224, at 232. On the other hand, ifthe measured pressure read by programmable controller 186 is greaterthan a predetermined pressure, programmable controller 186 directs thepump motor of pressure source 162 to turn on, at 234.

At 236, programmable controller 186 polls a pump timer application todetermine whether the pump timer is on. If the pump timer is not on,programmable controller 186 directs the pump timer to turn on, at 238.If the pump timer is on, programmable controller 186 determines whetherthe pump timer limit is exceeded, at 240. If programmable controller 186determines that the pump timer limit is not exceeded, a user maydetermine whether relief valve 174 at expandable cuff 142 is closed, at242. If relief valve 174 is open, fluid is released from expandable cuff142 via relief valve 174, at 244. Programmable controller 186 directspressure source 162 to apply positive pressure to expand expandable cuff142, at 246 and negative pressure within appendage chamber 102 andspecifically, within PCI 110.

At 248, positive pressure check valve 193 determines whether pressurewithin expandable cuff 142 is greater than the rating pressure forpositive pressure check valve 193 coupled to expandable cuff 142. If thepressure within expandable cuff 142 is greater than or equal to thecheck valve rating pressure, positive pressure check valve 193 will opento release fluid thereby reducing pressure within expandable cuff 142,at 250. If the pressure within expandable cuff 142 is less than thecheck valve rating pressure, programmable controller 186 directspressure source 162 to apply positive pressure to expand expandable cuff142, at 246 and negative pressure within appendage chamber 102 andspecifically, within PCI 110.

If, at 252, expandable cuff 142 is sealed and, at 254, PCI 110 is sealedto sealing pad 158, programmable controller 186 directs pressure source162 to apply negative pressure within appendage chamber 102, includingwithin PCI 110, at 256. At 258, if pressure within appendage chamber102, including PCI 110, is less than the check valve rating pressure fornegative pressure check valve 191 coupled to pressure source 162 andappendage chamber 102, including PCI 110, negative pressure check valve191 will open to release fluid thereby increasing pressure withinappendage chamber 102, including PCI 110, at 260. If the pressure withinappendage chamber 102, including PCI 110, is greater than the negativepressure check valve 191 rating pressure, programmable controller 186returns to A in FIG. 5.

If, at 240, programmable controller 186 determines that the pump timerlimit is exceeded, programmable controller directs display 114 todisplay an error message, at 262. Then, after B, programmable controller186 directs the pump motor of pressure source 162 to turn off anddirects the pump timer to reset, at 264. Finally, at 266, programmablecontroller 186 directs on or more components of apparatus 100 to shutdown and terminates the therapy session.

Referring now to FIG. 6, apparatus and method 280 for monitoringpressure and adjusting pressure within apparatus 100 are now described.As will be apparent to one of ordinary skill in the art, method 280 maybe embodied in program instructions stored on the memory of programmablecontroller 186 of FIG. 3 that, when executed by programmable controller186, cause programmable controller 186 and apparatus 100 to provide thefunctionality ascribed to them herein. The program instructions may befirmware or software downloaded onto the memory of programmablecontroller 186 or implemented as a program product and stored on atangible storage device such as machine-readable medium, e.g., tape,compact disk (CD), digital versatile disk (DVD), blu-ray disk (BD),external nonvolatile memory device, USB, cloud storage, or othertangible storage medium.

At 282, programmable controller 186 monitors the pressure withinappendage chamber 102, including within PCI 110, measured by negativepressure sensor 192. Preferably, programmable controller 186 monitorsthe negative pressure during a treatment at a predetermined samplingrate.

At 284, programmable controller 186 determines whether the pressuremeasured at 282 is outside a predetermined pressure range, e.g., above apredetermined pressure. The predetermined pressure range and/orpredetermined pressure may be programmed and stored in the controller'smemory. The predetermined pressure may be selected as a pressure wherenegative pressure is not suitable, e.g., too weak, for use in apparatus100. In one embodiment, the predetermined pressure is −30 mmHg.

If programmable controller 186 detects that the measured pressure isabove the predetermined pressure, programmable controller 186 directspressure source 162 to expand expandable cuff 142, at 286.Advantageously, expansion of expandable cuff 142 will enhance the sealaround a user's appendage to minimize PCI 110 leakage through appendageopening 108 and to help permit pressure source 162 within appendagechamber 102 to create and maintain a suitable negative pressure therein.

At 288, if programmable controller 186 detects that the measuredpressure is above the predetermined pressure for a predetermined periodof time, e.g. 60 seconds, apparatus 100 may send an alert to theuser/physician/caregiver, at 290. Sending an alert may include directingcontrol panel 106 to visibly and/or audibly alert the user. Sending analert may also include shutting down power to one or more components toapparatus 100 such thermal exchange member 104, pressure source 162,and/or power source 194.

If programmable controller 186 detects that the measured pressure is notabove the predetermined pressure, programmable controller continues tomonitor pressure at 282 until treatment is completed.

As discussed above, the methods and apparatus of the present inventionare intended to create or assist in maintaining vasodilation andenhancing the transfer to energy to an arteriovenous anastomosisvascular area in a mammal, deliver heating or cooling to a body core ofthe mammal using the dilated arteriovenous anastomosis vascular areapulled closer to the skin by negative pressure, and in heating mode maycontinue to deliver heat to the body core using the dilatedarteriovenous anastomosis vascular area to a body at normothermiapre-treatment or to a body at sub-normothermia pre-treatment such thatthe body core reaches normothermia. Applicant believes that continuingto deliver heat to the dilated arteriovenous anastomosis area to a bodyat normothermia, or to a body core that has reached normothermia, causessecondary vasodilation in other arteriovenous anastomosis and peripheralvascular areas throughout the entire body to dissipate the excess heatbeing infused by the apparatus. The rapid delivery by the circulatorysystem of the blood needed to fill these newly dilated heatexchange-vascular structures increases microvascular circulation,benefitting all organs (internal and peripheral) and the associatedautoimmune, neurological, lymphatic and endocrinal systems.

Applicant has discovered that the methods and apparatus of the presentinvention may be used to adjust viscosity of blood in a user. Forexample, it is expected that the methods and apparatus of the presentinvention may be used to deliver heating or cooling to blood flowingthrough the AVA at a temperature and for a duration, e.g., using thermalexchange member 104, sufficient to adjust a viscosity of blood in thehuman to alleviate a symptom associated with a number of autoimmune,circulatory, neurological, lymphatic, and/or endocrinal maladies, or anycombinations thereof. Without wishing to be bound by such theory as tothe mechanism of action, it is expected that the reduction of bloodviscosity increases microvascular circulation and alleviates asymptom(s) associated with all diseases or conditions associated withsystemic inflammation or hyperviscosity of the blood including, but notlimited to, hypertension, occlusive arterial disease, myocardialinfarction, kidney failure, hyperglycemia, preeclampsia, anddyslipidemia.

In addition, the methods and apparatus of the present invention may beused to reduce core body temperature for treatment of heart attack,stroke, heat stroke, reduction of fever including fever not resultingfrom an immune response.

As explained in U.S. Patent Application Publication No. 2012/0191022 toMuehlbauer, it is also expected that the methods and apparatus of thepresent invention may be used to treat a variety of neurologicalmaladies that have not previously been identified as treatable by thetherapeutic application of thermal energy. For example, it is expectedthat use of apparatus constructed in accordance with the principles ofthe present invention causes enhanced systemic circulation, which inturn causes redistribution of intracranial and peripheral blood flow.Without wishing to be bound by such theory as to the mechanism ofaction, it is expected that such redistribution may lead to varied flowpatterns in the brain, e.g., in the circulation in the Circle of Willis,thereby alleviating symptoms of neurological maladies such asParkinson's disease, migraines, Alzheimer's disease, bipolar disorder,schizophrenia, attention deficit disorder (ADD), attention deficithyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), andAutism.

It is also expected that increased circulation resulting from use ofapparatus constructed in accordance with the present invention willprovide several important benefits to patients suffering from poorperipheral circulation. For example, diabetic patients who maintain poorblood glucose control are known to suffer from poor peripheral bloodcirculation and neuropathy, often resulting in limb amputation,especially of toes. It is expected that treatments provided using theapparatus of the present invention will increase peripheral circulationin diabetic patients, thereby reducing the risk of occurrence ofgangrene requiring amputation. In addition, the enhanced peripheralcirculation is expected to reduce neuropathy in such patients, whichfurther reduces the risk of injury to peripheral limbs and appendagesnecessitating amputation.

It is expected that use of the methods and apparatus of the presentinvention also may promote wound healing by stimulating the lymphaticsystem. In particular, delivering heat to a normothermic person (aperson having approximately normal body temperature) has been observedto increase whole body circulation. While not wishing to be bound by anytheory as to the mechanism of action, it is believed that such increasedcirculation will also stimulate the lymphatic and endocrinal systems.With respect to the lymphatic system, which controls transmission ofintracellular fluids, an increase in blood circulation also is expectedto produce a corresponding increase in flow in the lymph system. For apatient suffering from chronic wounds, such as diabetic ulcers,stimulation of the lymphatic system is expected to improve flow ofexudate to the site of the chronic wound. Provided that steps are takento prevent pooling of exudate at the wound site (e.g., to preventbacterial growth), such increased exudate is expected to wash toxinsfrom the wound bed, and more quickly deliver materials (platelets andproteins) to the wound site that facilitate wound hearing.

Improved functioning of the lymph system resulting from use of theapparatus of the present invention also may be beneficial for patientssuffering from edema, for example, resulting from end-stage renaldisease or cirrhosis of the liver. In such patients, hypertensionresulting from declining kidney function and/or reduced liver functiondue to cirrhosis can result in the buildup of excess interstitial fluidin the abdomen and legs. It is believed that by increasing whole bodycirculation in accordance with the present invention, multiple benefitsmay be achieved. First, increased whole body circulation is expected toresult from vasodilation of peripheral heat exchange vessels, therebyallowing blood to fill those vessels and reduce hypertension. Second,the increased blood flow is expected to stimulate the lymphatic system,possibly facilitating the removal and processing of interstitial fluidsand reducing edema. While not believed to be curative, use of theapparatus of the present invention with such patients on a regularbasis, e.g., once or twice per day, may be palliative and improve thepatient's quality of life.

While not wishing to be bound by any theory as to the mechanism ofaction, the present invention is believed to affect core bodytemperature by dilating or maintaining dilation in one or morearteriovenous anastomoses (AVAs) in the subject by applying a continuoustemperature gradient that infuses heat into or extracts heat from theblood in the AVA vascular area pulled closer to the skin by negativepressure that is then circulated by the heart. Thermoregulatory feedbackmechanisms are likely also implicated, by stimulating heat transfer atthe core and/or head in response to increases in temperature elsewherein the body. Whatever the mechanism of action, use of the invention toapply heat to the skin at a location on the body remote from theintended treatment site (e.g., to the extremities to thermoregulate coreor cranial temperatures) produces heat transfers at the body core totherapeutic levels.

It is further believed that use of the methods of the invention willhave an effect on metabolic processes in the body by affecting theactivity of certain enzymes and hormones. For example, thethermoregulatory changes produced by use of the invention may influencethe activity of enzymes involved in pain, such as prostaglandin-Esynthesizing (PEGS) enzymes, COX enzymes (1, 2 and/or 3), and/ormicrosomal PEGS-1 (mPEGS), most likely by increasing enzyme kineticsslowed by abnormally low core body temperatures. In metabolic disorderssuch as hypothyroidism, the body temperature is lowered and enzymefunction decreases, slowing metabolism and leading to weight gain andfatigue. Raising body temperature according to the invention may restorethe enzymes' kinetic rate and positively affect metabolic disorders.

Patients in a pre-diabetic or diabetic state, as clinically measuredfrom blood glucose and/or AlC levels in the subject over time, mayexperience increased weight loss using of the methods of the invention.Insulin dependent diabetics may find their need for insulin reduced by60 to 70% within a relatively short period of time. Again, while notwishing to be bound by any theory as to mechanism of action, thepotential impact on metabolic processes as described herein may be inplay in pre-diabetic and diabetic individuals, in whom core bodytemperatures may become sub-normothermic over time or normothermicindividuals that may benefit from increased circulation.

The biological responses produced by use of the invention havetherapeutic implications for a further range of conditions. For example,migraines, chronic fatigue syndrome, and certain autoimmune disordersshare symptoms with autonomic and sympathetic nervous system (SNS)hypofunction. The SNS controls blood vessel constriction, decreasingblood flow to extremities when activated. Warmed blood from the heartwill first warm the SNS nerve nexus behind the heart. This SNS influencemay then reverse the SNS hypofunction and in turn reverse the symptomsof the condition being treated. Therefore, in preferred embodiments, theinvention may be used to treat migraines and also to reduce theincidence of pre-migraine events, such as prodromes and auras.

Thermal energy also may to be removed from the head to providebeneficial effects. In some embodiments, thermal energy is removed fromthe head arterial blood supply, e.g., carotid arterial blood. Those ofordinary skill in the clinical arts will be familiar with or may readilyascertain other measures for beneficial improvements in the condition oftreated patients; e.g., reductions in body mass, improvements inneurological function as evidenced by motor function test results, andthe like.

In addition, circulatory disorders associated with vasoconstriction inthe extremities (such as carpal tunnel syndrome, trigger finger andarthritis) may be treated. Treatment of dermatological disordersassociated with restricted blood flow to the skin (such as eczema) mayalso be effected by increasing the local flow of blood and oxygen to atreatment site. Disorders known to disrupt thermoregulatory processessuch as stress, anxiety, neurodegenerative conditions such as multiplesclerosis and fibromyalgia, as well as sequalae of chemotherapy(affecting digestion) and irritable bowel syndrome (affecting bowelregularity) may also be beneficially affected by use of the invention.

The above described thermal energy treatments may be performed with orwithout the aid of automated data collection devices and/or processors.As such, in certain embodiments one or more sensors are employed todetect temperatures in the core body and head region of the mammal. Anyconvenient temperature sensing devices may be employed, where suitabledevices include: thermocouples, thermistors, microwave temperaturesensors, infrared cameras, and the like. The position and nature of thetemperature sensing devices necessarily depends on whether it is todetect the core body or head temperature of the mammal. For detectingthoracic/abdominal core body temperature, sensor locations of interestinclude: the esophagus, the rectum, and in the case of microwavedetection, anywhere on the surface of the body to measure the underlyingtemperature. For head temperature, sensor locations of interest include:the auditory canal, the oral cavity, and in the case of microwavedetection, anywhere on the surface of the head to measure the underlyingtemperature.

The data collected from these sensor devices may be processed by aprocessor to at least display the data for the operator in a userfriendly/readable format. The data may also be processed by a processorwhich causes or inhibits the thermal energy transfer events in responseto the detected data or variations therein.

Examples of the practice of the invention are set forth below. Theseexamples shall not be considered to limit the invention, whose scope isdefined by the appended claims.

Example 1 Blood Viscosity Adjustment

A beneficial improvement in reducing blood viscosity of human patientswas confirmed by blood testing when undergoing a heating treatment inaccordance with the present invention. Six vials of blood were drawnfrom a patient's left arm before treatment on the right hand, and sixvials of blood were drawn from the patient's left arm followingtreatment. The patient underwent a first treatment using a previouslyknown device, referred to as “Machine 1”, and, at a later date,underwent a second treatment using apparatus and methods describedherein in accordance with the present invention, referred to as “Machine2”.

Patient Treatment 1/Machine 1 Treatment 2/Machine 2 Pre- Post- Pre-Post- Treatment Treatment Treatment Treatment Systolic Viscosity 38.536.8 36.7 32.8 Diastolic Viscosity 110.8 103.1 98.7 87.2

The test results show a 4.42% reduction in systolic viscosity and a6.95% reduction in diastolic viscosity after the first 20 minutetreatment using the previously known device. After the second 20 minutetreatment, nine days later, the test results reveal an 18.41% reductionin systolic viscosity and a 21.3% reduction in diastolic viscosity usingapparatus and methods in accordance with the present invention. As willbe apparent to one of ordinary skill in the art, treatment usingapparatus and methods in accordance with the present invention providesa dramatic blood viscosity reduction.

Example 2 Blood Viscosity Adjustment

FIGS. 7A and 7B are images from a microscope of red blood cells within ablood sample taken from the hand opposite the treatment hand of apatient. Before treatment, the red blood cells were bunched together(rouleaux formation) as shown in FIG. 7A. Rouleaux affects properoxygenation because the red blood cells do not circulate well enough todeliver oxygen where it is needed. Conditions which cause rouleauxformation include infections, inflammatory and connective tissuedisorders, and cancers. It also occurs in diabetes mellitus and is oneof the causative factors for microvascular occlusion in diabeticretinopathy. After a 20 minute warming treatment using methods inaccordance with the present invention, the red blood cells becomesymptomatic of healthy blood, as shown in FIG. 7B. Without wishing to bebound by such theory as to the mechanism of action, it is expected thatthe healthy red blood cells are the result of a reduction in patientblood viscosity thereby rapidly increasing microvascular circulation,oxygenation and protein delivery to alleviate symptom(s) associated withall diseases or conditions associated with systemic inflammation orhyperviscosity of the blood.

Example 3 Blood Viscosity Adjustment

FIGS. 8A and 8B are images from a microscope of red blood cells within ablood sample taken from the hand opposite the treatment hand of anotherpatient treated in accordance with methods of the present invention,before and after treatment, respectively. Consistent with the resultsdescribed above with respect to FIGS. 7A and 7B, FIG. 8B shows that thered blood cells present healthy characteristics after a 20 minutewarming treatment using apparatus and methods in accordance with thepresent invention, as compared to the rouleaux alignment of red bloodcells pre-treatment in FIG. 8A.

Example 4 Fibromyalgia

In an Independent Review Board controlled proof of concept studyconducted by the US Department of Veterans Affairs and the University ofSan Diego, Calif., five patients having physician diagnosed fibromyalgiaunderwent one heating treatment per day for 10 minutes over 28 days, inaccordance with the methods of the present invention. The reportedresults are in the Table below.

Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Pre Post Pre Post PrePost Pre Post Pre Post Widespread 15 13 13 13 15  8 18 17 16 14 PainIndex Tender 12  8 14  6 15 14 18 17 18 18 Point Count Depression SevereModerate Minimal Minimal Minimal Minimal Mild Minimal Severe Severe

As may be observed from studying the Table, four patients reportedimprovement in Widespread Pain Index while one patient demonstrated noimprovement; four patients reported a reduction in Tender Point Countwith the reduction of Patient 1 and 2 being so significant that they nolonger met the fibromyalgia diagnosis criteria minimum tender pointcount of 11, while one patient showed no improvement; and two patientsreported improvement in Depression while three patients reported noimprovement.

While various illustrative embodiments of the invention are describedabove, it will be apparent to one skilled in the art that variouschanges and modifications may be made therein without departing from theinvention. The appended claims are intended to cover all such changesand modifications that fall within the true scope of the apparatus andmethods of the present invention.

1. Apparatus for treating a condition of a human, the apparatuscomprising: an appendage chamber configured to accept a human appendagecontaining an arteriovenous anastomosis (AVA); a thermal exchange memberdisposed within the appendage chamber, the thermal exchange memberconfigured to selectively heat or cool blood flowing through the AVA; aload sensor coupled to the thermal exchange member, the load sensorconfigured to measure a force of the appendage applied to the thermalexchange member; a pressure source coupled to the appendage chamber andconfigured to apply negative pressure within the appendage chamber; anda programmable controller configured to: determine a base force measuredusing the load sensor, calculate and set a force range using the baseforce, monitor whether the force of the appendage measured by the loadsensor falls within the force range, send an alert if the force isoutside the force range, and adjust the force range over time toaccommodate ambient temperature variations caused by heating or coolingthe thermal exchange member.
 2. The apparatus of claim 1, wherein theappendage chamber comprises an expandable cuff with an appendage openingconfigured to accept the appendage, wherein the pressure source isconfigured to apply positive pressure to expand the expandable cuff toseal around the appendage.
 3. The apparatus of claim 2, furthercomprising a flexible membrane having a membrane opening configured toaccept the appendage, wherein the flexible membrane conforms to theexpandable cuff as the pressure source applies positive pressure.
 4. Theapparatus of claim 2, wherein the appendage chamber comprises a pressurechamber insert having the expandable cuff, wherein the pressure chamberinsert is configured to be removable from the appendage chamber.
 5. Theapparatus of claim 1, wherein the thermal exchange member comprises aPeltier or electric heating device.
 6. Apparatus for treating acondition of a human, the apparatus comprising: an appendage chamberhaving an expandable cuff with an appendage opening configured to accepta human appendage containing an arteriovenous anastomosis (AVA); athermal exchange member disposed within the appendage chamber, thethermal exchange member configured to selectively heat or cool bloodflowing through the AVA; a pressure source disposed within the appendagechamber and comprising a single motor-driven pump, the pump coupled viaan opening to the appendage chamber and coupled via a pressure line tothe expandable cuff, the pump configured to simultaneously applynegative pressure to the appendage chamber and apply positive pressureto the pressure line to expand the expandable cuff to seal around theappendage, when the appendage is placed within the appendage chamber; anegative pressure sensor configured to measure a pressure within theappendage chamber; and a programmable controller configured to: monitorthe pressure measured by the negative pressure sensor, and direct thepressure source to expand the expandable cuff if the measured pressureis above a predetermined pressure without measuring pressure within theexpandable cuff.
 7. The apparatus of claim 6, further comprising aflexible membrane having a membrane opening configured to accept theappendage, wherein the flexible membrane conforms to the expandable cuffas the pump applies positive pressure.
 8. The apparatus of claim 6,wherein the appendage chamber comprises a pressure chamber insert havingthe expandable cuff, wherein the pressure chamber insert is configuredto be removable from the appendage chamber.
 9. The apparatus of claim 8,further comprising a sealing pad disposed within the appendage chamber,the sealing pad having a sealing pad opening configured to be disposedaround the thermal exchange member, wherein the sealing pad isconfigured to be coupled to the pressure chamber insert to enhanceapplication of negative pressure therein.
 10. The apparatus of claim 6,further comprising a deformable pad disposed within the appendagechamber, the deformable pad configured to contact the appendage and theappendage chamber to urge the appendage onto the thermal exchangemember.
 11. The apparatus of claim 6, further comprising a load sensorcoupled to the thermal exchange member, the load sensor configured tomeasure a force of the appendage applied to the thermal exchange member.12. The apparatus of claim 6, wherein the programmable controller isconfigured to monitor application of negative pressure within theappendage chamber responsive to the pressure measured by the negativepressure sensor.
 13. The apparatus of claim 6, wherein the thermalexchange member is configured to heat or cool the blood at a temperatureand for a duration sufficient to adjust a viscosity of the blood. 14.The apparatus of claim 6, wherein the programmable controller isconfigured to control heating or cooling of the thermal exchange memberresponsive to user input or a preselected therapy regime.
 15. Theapparatus of claim 14, wherein the preselected therapy regime isselected to alleviate a symptom associated with an autoimmune,circulatory, neurological, lymphatic, thermoregulatory disorders, orendocrinal dysfunction, or any combination thereof including Parkinson'sdisease, diabetic neuropathy, migraine headaches, Alzheimer's disease,arthritis, fibromyalgia, Lyme disease, bipolar disorder, schizophrenia,attention deficit disorder (ADD), attention deficit hyperactivitydisorder (ADHD), obsessive compulsive disorder (OCD), Autism, andhyperviscosity.
 16. A method for adjusting viscosity of blood, themethod comprising: providing an appendage chamber, a thermal exchangemember disposed within the appendage chamber, and a pressure sourcecoupled to the appendage chamber; disposing a human appendage containingan arteriovenous anastomosis (AVA) within the appendage chamber;applying negative pressure in the appendage chamber using the pressuresource; and heating or cooling the thermal exchange member to deliverheating or cooling to blood flowing through the AVA at a temperature andfor a duration sufficient to adjust a viscosity of the blood toalleviate a symptom associated with at least one of an autoimmune,circulatory, neurological, lymphatic, thermoregulatory, or endocrinalmalady.
 17. The method of claim 16, wherein the heating or coolingcomprises heating or cooling the thermal exchange member to deliverheating or cooling for approximately five to thirty minutes.
 18. Themethod of claim 16, wherein the heating comprises heating the thermalexchange member to between 100-120° F. and the cooling comprises coolingthe thermal exchange member to between 58-95° F.
 19. The method of claim16, wherein applying negative pressure further comprises maintaining thenegative pressure between −1 mmHg and −50 mmHg.
 20. The method of claim16, wherein the adjustment in viscosity of the blood increasesmicrovascular circulation and alleviates a symptom associated withhypertension, occlusive arterial disease, myocardial infarction, kidneyfailure, liver failure, hyperglycemia, preeclampsia, dyslipidemia, anddiseases or conditions associated with systemic inflammation orhyperviscosity of the blood.